KCNH2 Variant A172V

Summary of observed carriers, functional annotations, and structural context for KCNH2 A172V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

32%

3/11 effective observations

Total carriers

1

1 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

A172V has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 0% of WT with a standard error of 0%. In our analysis we used SE < 20% as 'high quality'. Approximately below 50% of WT is considered PS3 moderate and below 30% is PS3 strong.

Variant features alone are equivalent to phenotyping 2 individuals with LQT2 and 8 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-0.608 0.196 0 0.445 85

PROVEAN scores below -2 suggest deleterious impact. REVEL scores above 0.5–0.75 are often interpreted as likely pathogenic. PolyPhen-2 scores above 0.85 are typically pathogenic. BLAST-PSSM reflects evolutionary conservation; more negative values indicate rarer substitutions. Penetrance density summarises neighbouring residue risk (Kroncke et al. 2019).

Reported carrier data

Observed carriers by publication or cohort.
Source Year Carriers Unaffected LQT2 Other Disease
24667783 2015 1 0 1
Literature, cohort, and gnomAD – 1 0 1 –
Variant features alone – 10 8 2 –

Totals may differ from individual publications due to duplicate patients removed during curation.

Nearby variants

Neighbouring residues within 15 Ångström provide structural context. Variants listed in the right-most column have been observed clinically or in gnomAD. Note that some residues appear multiple times at different distances since the functional KV11.1 channel (protein product of KCNH2/hERG) is a homotetramer and occasionally the same residue from multiple subunits is present within the 15Å window.

Previously observed variants near A172V.
Neighbour residue Distance (Å) Observed variants
172 0 A172V,
171 4 L171Ins,
173 4
170 5 L170Ins,
174 5
169 7 A169G,
175 7 A175S, A175D, A175X,
168 8
176 8 R176Q, R176W, R176X,
167 8
177 8 E177X,
166 9
178 9
165 10
179 10 S179W,
164 11 R164H, R164C,
180 11
163 11
181 11 R181fsX, R181Q, R181W,
162 12 T162X,
182 12 S182X,
161 13
183 13 G183fsX,
160 13
184 13 G184Del,
159 14
185 14
158 14
186 14 G186fsX,
157 15 P157X,
187 15 G187Del, G187S, G187A, G187X,